The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum

The concept of schizophrenia only covers the 30% poor outcome fraction of a much broader multidimensional psychotic syndrome, yet paradoxically has become the dominant prism through which everything ‘psychotic’ is observed, even affective states with mild psychosis labelled ‘ultra-high risk’ (for schizophrenia). The inability of psychiatry to frame psychosis as multidimensional syndromal variation of largely unpredictable course and outcome – within and between individuals – hampers research and recovery-oriented practice. ‘Psychosis’ remains firmly associated with ‘schizophrenia’, as evidenced by a vigorous stream of high-impact but non-replicable attempts to ‘reverse-engineer’ the hypothesized biological disease entity, using case–control paradigms that cannot distinguish between risk for illness onset and risk for poor outcome. In this paper, the main issues surrounding the concept of schizophrenia are described. We tentatively conclude that with the advent of broad spectrum phenotypes covering autism and addiction in DSM5, the prospect for introducing a psychosis spectrum disorder – and modernizing psychiatry – appears to be within reach.

[1]  J. van os,et al.  Psychotic experiences and risk of self-injurious behaviour in the general population: a systematic review and meta-analysis , 2015, Psychological Medicine.

[2]  Godfrey D Pearlson,et al.  Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. , 2003, Schizophrenia bulletin.

[3]  Brian Kirkpatrick,et al.  The NIMH-MATRICS consensus statement on negative symptoms. , 2006, Schizophrenia bulletin.

[4]  J. Os,et al.  Testing the hypothesis that psychotic illness begins when subthreshold hallucinations combine with delusional ideation , 2012, Acta psychiatrica Scandinavica.

[5]  A. Young,et al.  A comparison of schizophrenia, schizoaffective disorder, and bipolar disorder: Results from the Second Australian national psychosis survey. , 2015, Journal of affective disorders.

[6]  R. Kessler,et al.  The Bidirectional Associations Between Psychotic Experiences and DSM-IV Mental Disorders. , 2016, The American journal of psychiatry.

[7]  J. Os,et al.  Is our concept of schizophrenia influenced by Berkson’s bias? , 2004, Social Psychiatry and Psychiatric Epidemiology.

[8]  J. Os,et al.  An updated and conservative systematic review and meta-analysis of epidemiological evidence on psychotic experiences in children and adults: on the pathway from proneness to persistence to dimensional expression across mental disorders , 2012, Psychological Medicine.

[9]  R. Murray A REAPPRAISAL OF AMERICAN PSYCHIATRY , 1979, The Lancet.

[10]  J. Os,et al.  Evidence that the outcome of developmental expression of psychosis is worse for adolescents growing up in an urban environment , 2006, Psychological Medicine.

[11]  N. Andreasen The American concept of schizophrenia. , 1989, Schizophrenia bulletin.

[12]  Miles Be,et al.  Letter: Serum-phenytoin. , 1976 .

[13]  Peter B. Jones,et al.  Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial , 2012, BMJ : British Medical Journal.

[14]  H. Meltzer,et al.  Effect of diagnostic criteria on the ratio of male to female schizophrenic patients. , 1984, The American journal of psychiatry.

[15]  M. Keshavan,et al.  Schizophrenia, “Just the Facts” 6. Moving ahead with the schizophrenia concept: From the elephant to the mouse , 2011, Schizophrenia Research.

[16]  J. Suvisaari,et al.  Lifetime prevalence of psychotic and bipolar I disorders in a general population. , 2007, Archives of general psychiatry.

[17]  A. Thompson,et al.  Views of early psychosis clinicians on discontinuation of antipsychotic medication following symptom remission in first episode psychosis , 2016, Early intervention in psychiatry.

[18]  J. Os,et al.  Subclinical psychosis and depression: Co-occurring phenomena that do not predict each other over time , 2011, Schizophrenia Research.

[19]  A. Caspi,et al.  Children's self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study. , 2000, Archives of general psychiatry.

[20]  Jim van Os,et al.  Evidence that psychotic symptoms are prevalent in disorders of anxiety and depression, impacting on illness onset, risk, and severity--implications for diagnosis and ultra-high risk research. , 2012, Schizophrenia bulletin.

[21]  N. Andreasen,et al.  Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. , 2005, The American journal of psychiatry.

[22]  L. Krabbendam,et al.  Impact of psychological trauma on the development of psychotic symptoms: relationship with psychosis proneness , 2006, British Journal of Psychiatry.

[23]  J. Os,et al.  Dimensions of depression, mania and psychosis in the general population , 2004, Psychological Medicine.

[24]  J. McGrath,et al.  A Systematic Review of the Prevalence of Schizophrenia , 2005, PLoS medicine.

[25]  J. van os,et al.  Affective dysregulation and reality distortion: a 10-year prospective study of their association and clinical relevance. , 2011, Schizophrenia bulletin.

[26]  James G. Scott,et al.  The association between general psychological distress and delusional-like experiences: A large population-based study , 2011, Schizophrenia Research.

[27]  J. van Os,et al.  “Schizophrenia” does not exist , 2016, BMJ : British Medical Journal.

[28]  E. Bromet,et al.  Long-term diagnostic stability and outcome in recent first-episode cohort studies of schizophrenia. , 2005, Schizophrenia bulletin.

[29]  R. Murray,et al.  Psychotic experiences in the general population: A twenty-year prospective community study , 2007, Schizophrenia Research.

[30]  R. Murray,et al.  The Myth of Schizophrenia as a Progressive Brain Disease , 2012, Schizophrenia bulletin.

[31]  B. George,et al.  A modern name for schizophrenia (PSS) would diminish self-stigma , 2013, Psychological Medicine.

[32]  J. van os,et al.  The incidence and outcome of subclinical psychotic experiences in the general population. , 2005, The British journal of clinical psychology.

[33]  J. Ioannidis Why Most Published Research Findings Are False , 2005, PLoS medicine.

[34]  Pamela B. Mahon,et al.  Predictors of lithium response in bipolar disorder , 2011, Therapeutic advances in chronic disease.

[35]  R. Murray,et al.  Schizophrenia is not disappearing in South West Scotland , 2000, Schizophrenia Research.

[36]  J. van os,et al.  Early expression of negative/disorganized symptoms predicting psychotic experiences and subsequent clinical psychosis: a 10-year study. , 2010, The American journal of psychiatry.

[37]  A. Farmer,et al.  Evaluation of the validity and utility of a transdiagnostic psychosis dimension encompassing schizophrenia and bipolar disorder. , 2016, The British journal of psychiatry : the journal of mental science.

[38]  P. McGorry,et al.  Response to Jorm: Headspace – A national and international innovation with lessons for redesign of mental health care in Australia , 2016, The Australian and New Zealand journal of psychiatry.

[39]  Jim van Os,et al.  Redeeming diagnosis in psychiatry: timing versus specificity , 2013, The Lancet.

[40]  J. van os,et al.  Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience , 2017, Psychological Medicine.

[41]  S. Guze,et al.  Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. , 1970, The American journal of psychiatry.

[42]  J. Strauss,et al.  Flexible System for the Diagnosis of Schizophrenia: Report from the WHO International Pilot Study of Schizophrenia , 1973, Science.

[43]  R. de Graaf,et al.  Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness–persistence model , 2007, Psychological Medicine.

[44]  S. Galderisi,et al.  Deficit schizophrenia: an update , 2008, World psychiatry : official journal of the World Psychiatric Association.

[45]  R. Hoffman,et al.  The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis I. Study rationale and design , 2003, Schizophrenia Research.

[46]  R. Kahn,et al.  Sex differences in the risk of schizophrenia: evidence from meta-analysis. , 2003, Archives of general psychiatry.

[47]  Tyrone D. Cannon,et al.  Anxiety in youth at clinical high risk for psychosis , 2017, Early intervention in psychiatry.

[48]  J. Os,et al.  Evidence that onset of clinical psychosis is an outcome of progressively more persistent subclinical psychotic experiences: an 8-year cohort study. , 2011, Schizophrenia bulletin.

[49]  J. V. Snellenberg,et al.  Meta-analytic Evidence for Familial Coaggregation of Schizophrenia and Bipolar Disorder , 2009 .

[50]  S. Saha,et al.  A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? , 2007, Archives of general psychiatry.

[51]  Thomas R Insel,et al.  Toward new approaches to psychotic disorders: the NIMH Research Domain Criteria project. , 2010, Schizophrenia bulletin.

[52]  G. Malhi,et al.  Swan song for schizophrenia? , 2014, The Australian and New Zealand journal of psychiatry.

[53]  P. Corrigan,et al.  Influence of schizophrenia diagnosis on providers' practice decisions. , 2015, The Journal of clinical psychiatry.

[54]  I. Gottesman,et al.  The Schizophrenia Construct After 100 Years of Challenges , 2011 .

[55]  Akira Sawa,et al.  Schizophrenia: Diverse Approaches to a Complex Disease , 2002, Science.

[56]  J. Veijola,et al.  A systematic review and meta-analysis of recovery in schizophrenia. , 2013, Schizophrenia bulletin.

[57]  P. Delespaul,et al.  Toward a world consensus on prevention of schizophrenia , 2005, Dialogues in clinical neuroscience.

[58]  Jared X. Van Snellenberg,et al.  Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. , 2009, Archives of general psychiatry.

[59]  J. Lieberman,et al.  Reconsidering the Classification of Schizophrenia and Manic Depressive Illness — A Critical Analysis and Mew Conceptual Model , 2003, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[60]  Godfrey D Pearlson,et al.  Gray matter volume as an intermediate phenotype for psychosis: Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). , 2013, The American journal of psychiatry.

[61]  H. Kraemer,et al.  DSM categories and dimensions in clinical and research contexts , 2007, International journal of methods in psychiatric research.

[62]  J. Waddington,et al.  Developmental trajectory and disease progression in schizophrenia: the conundrum, and insights from a 12-year prospective study in the Monaghan 101 , 1997, Schizophrenia Research.

[63]  J. Read,et al.  Making Sense of Madness: Contesting the Meaning of Schizophrenia , 2009 .

[64]  P. Fox,et al.  Identification of a common neurobiological substrate for mental illness. , 2015, JAMA psychiatry.

[65]  R. Murray,et al.  Association between symptom dimensions and categorical diagnoses of psychosis: a cross-sectional and longitudinal investigation. , 2014, Schizophrenia bulletin.

[66]  P. McGorry,et al.  Why We Need a Transdiagnostic Staging Approach to Emerging Psychopathology, Early Diagnosis, and Treatment. , 2016, JAMA psychiatry.

[67]  P. Cohen,et al.  The clinician's illusion. , 1984, Archives of general psychiatry.

[68]  I. Brockington Schizophrenia: yesterday's concept , 1992, European Psychiatry.

[69]  J. Strauss,et al.  Choosing an approach for diagnosing schizophrenia. , 1977, Archives of general psychiatry.

[70]  Hok Pan Yuen,et al.  Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. , 2002, Archives of general psychiatry.

[71]  M. Fava,et al.  Association between bipolar spectrum features and treatment outcomes in outpatients with major depressive disorder. , 2010, Archives of general psychiatry.

[72]  C. Wasserman,et al.  Clinicopathological significance of psychotic experiences in non-psychotic young people: evidence from four population-based studies , 2012, British Journal of Psychiatry.

[73]  A. Gagnon,et al.  Influence of diagnostic classification on gender ratio in schizophrenia , 2004, Social Psychiatry and Psychiatric Epidemiology.

[74]  C. Waternaux,et al.  One hundred years of schizophrenia: A meta-analysis of the outcome literature , 1993, Schizophrenia Research.

[75]  K. Takemura,et al.  Impact of changing the Japanese term for “schizophrenia” for reasons of stereotypical beliefs of schizophrenia in Japanese youth , 2009, Schizophrenia Research.

[76]  Denny Borsboom,et al.  A Network Approach to Environmental Impact in Psychotic Disorder: Brief Theoretical Framework. , 2016, Schizophrenia bulletin.

[77]  T. Insel,et al.  Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? , 2012, Molecular Psychiatry.

[78]  R. Bentall,et al.  Testing the psychopathology of psychosis: evidence for a general psychosis dimension. , 2013, Schizophrenia bulletin.

[79]  Peter B. Jones,et al.  Combining dimensional and categorical representation of psychosis: the way forward for DSM-V and ICD-11? , 2009, Psychological Medicine.

[80]  Jianxin Shi,et al.  Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs , 2013, Nature Genetics.

[81]  R. Bentall,et al.  Abandoning the concept of 'schizophrenia': some implications of validity arguments for psychological research into psychotic phenomena. , 1988, The British journal of clinical psychology.

[82]  W. Carpenter,et al.  Deficit and nondeficit forms of schizophrenia: the concept. , 1988, The American journal of psychiatry.

[83]  J. Os,et al.  SUPPLEMENTARY TO : Seeking verisimilitude in a class : A systematic review of evidence that the criterial clinical symptoms of schizophrenia are taxonic , 2008 .

[84]  R. Kendell,et al.  Distinguishing between the validity and utility of psychiatric diagnoses. , 2003, The American journal of psychiatry.

[85]  R. Murray,et al.  Biological, life course, and cross-cultural studies all point toward the value of dimensional and developmental ratings in the classification of psychosis. , 2007, Schizophrenia bulletin.

[86]  K. Kendler Phenomenology of Schizophrenia and the Representativeness of Modern Diagnostic Criteria. , 2016, JAMA psychiatry.

[87]  J. van os,et al.  A critique of the “ultra‐high risk” and “transition” paradigm , 2017, World psychiatry : official journal of the World Psychiatric Association.

[88]  A. Yung,et al.  Mapping the Onset of Psychosis: The Comprehensive Assessment of At-Risk Mental States , 2005 .

[89]  Denis English,et al.  Notes of a biology watcher , 2009 .

[90]  G. Pearlson,et al.  Sex differences in schizophrenia. , 1997, Archives of general psychiatry.

[91]  J. Os,et al.  Do subthreshold psychotic experiences predict clinical outcomes in unselected non-help-seeking population-based samples? A systematic review and meta-analysis, enriched with new results , 2012, Psychological Medicine.

[92]  J. Os,et al.  The Natural History of the Course and Outcome of Schizophrenia , 2010 .

[93]  J. Shields,et al.  A polygenic theory of schizophrenia. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Jeffrey A. Cohen,et al.  Defining the clinical course of multiple sclerosis: the 2013 revisions. , 2014, Neurology.

[95]  J. Os,et al.  Psychotic experiences and incident suicidal ideation and behaviour: Disentangling the longitudinal associations from connected psychopathology , 2016, Psychiatry Research.

[96]  Sukanta Saha,et al.  A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology , 2004, BMC medicine.

[97]  J. van os,et al.  Lessons learned from the psychosis high-risk state: towards a general staging model of prodromal intervention , 2013, Psychological Medicine.

[98]  Effect of Name Change of Schizophrenia on Mass Media Between 1985 and 2013 in Japan: A Text Data Mining Analysis. , 2016, Schizophrenia bulletin.

[99]  J. Read,et al.  Negative childhood experiences and mental health: theoretical, clinical and primary prevention implications , 2012, British Journal of Psychiatry.

[100]  K. Kendler The transformation of American psychiatric nosology at the dawn of the twentieth century , 2016, Molecular Psychiatry.

[101]  R. Murray,et al.  Diagnostic value of the DSM and ICD categories of psychosis: an evidence-based approach , 2000, Social Psychiatry and Psychiatric Epidemiology.

[102]  J. van os,et al.  Psychosis as a transdiagnostic and extended phenotype in the general population , 2016, World psychiatry : official journal of the World Psychiatric Association.

[103]  Robin M. Murray,et al.  A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder , 2004, Schizophrenia Research.

[104]  R. Bentall,et al.  The Psychosis Continuum: Testing a Bifactor Model of Psychosis in a General Population Sample , 2017, Schizophrenia bulletin.

[105]  J. van Os,et al.  The dynamics of subthreshold psychopathology: implications for diagnosis and treatment. , 2013, The American journal of psychiatry.

[106]  J. Os A salience dysregulation syndrome , 2022 .

[107]  J. Os,et al.  A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness–persistence–impairment model of psychotic disorder , 2008, Psychological Medicine.

[108]  J. Os,et al.  Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people , 2004, BMJ : British Medical Journal.

[109]  J. Moncrieff,et al.  Schizophrenia: a critical psychiatry perspective , 2015, Current opinion in psychiatry.

[110]  I. Levav,et al.  Self-reported attenuated psychotic symptoms as forerunners of severe mental disorders later in life. , 2012, Archives of general psychiatry.

[111]  M. Slade,et al.  Conceptual framework for personal recovery in mental health: systematic review and narrative synthesis , 2011, British Journal of Psychiatry.

[112]  J. Ayuso-Mateos,et al.  Evidence for the early clinical relevance of hallucinatory‐delusional states in the general population , 2013, Acta psychiatrica Scandinavica.

[113]  J. van os,et al.  Evidence that the presence of psychosis in non-psychotic disorder is environment-dependent and mediated by severity of non-psychotic psychopathology , 2015, Psychological Medicine.

[114]  A. Lasalvia,et al.  Should the label "schizophrenia" be abandoned? , 2015, Schizophrenia Research.

[115]  Godfrey D Pearlson,et al.  Neuropsychological impairments in schizophrenia and psychotic bipolar disorder: findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. , 2013, The American journal of psychiatry.

[116]  R. Murray,et al.  Sex and Schizophrenia: Effects of Diagnostic Stringency, and Associations with Premorbid Variables , 1993, British Journal of Psychiatry.

[117]  J. Strauss,et al.  Chronicity in schizophrenia: fact, partial fact, or artifact? , 1987, Hospital & community psychiatry.

[118]  Peter B. Jones,et al.  EARLY DETECTION AND INTERVENTION EVALUATION FOR PEOPLE AT-RISK OF PSYCHOSIS , 2012, Schizophrenia Research.

[119]  K. Nuechterlein,et al.  Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: A meta-analysis , 2009, Schizophrenia Research.

[120]  R. Murray,et al.  Mistakes I Have Made in My Research Career. , 2016, Schizophrenia bulletin.

[121]  A. Arntz,et al.  Subclinical psychotic experiences and bipolar spectrum features in depression: association with outcome of psychotherapy , 2013, Psychological Medicine.

[122]  J. Os,et al.  Follow-up studies of schizophrenia I: Natural history and non-psychopathological predictors of outcome , 1997, European Psychiatry.

[123]  S. Vukusic,et al.  Natural history of multiple sclerosis: a unifying concept. , 2006, Brain : a journal of neurology.

[124]  T. McGlashan A selective review of recent North American long-term followup studies of schizophrenia. , 1988, Schizophrenia bulletin.

[125]  Christos Pantelis,et al.  Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study , 2009, British Journal of Psychiatry.

[126]  S. Saha,et al.  Meta‐analyses of the incidence and prevalence of schizophrenia: conceptual and methodological issues , 2008, International journal of methods in psychiatric research.

[127]  John Torous,et al.  #Schizophrenia: Use and misuse on Twitter , 2015, Schizophrenia Research.

[128]  M. Tohen,et al.  One hundred years of schizophrenia: a meta-analysis of the outcome literature. , 1994 .

[129]  R. de Graaf,et al.  The impact of subclinical psychosis on the transition from subclinicial mania to bipolar disorder. , 2007, Journal of affective disorders.

[130]  Assen Jablensky,et al.  PAGES_DCNS 46_5.qxd:DCNS#45 , 2010 .

[131]  Tyrone D. Cannon,et al.  Treatment Precedes Positive Symptoms in North American Adolescent and Young Adult Clinical High Risk Cohort , 2018, Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53.

[132]  W. Carpenter Fifty Years: Do Over or Move Forward. , 2017, Schizophrenia bulletin.

[133]  Nigel Lester,et al.  Madness Explained: Psychosis and Human Nature , 2003, BMJ : British Medical Journal.

[134]  Kimberly B. Roth,et al.  Psychotic experiences and risk of death in the general population: 24–27 year follow-up of the Epidemiologic Catchment Area study , 2015, British Journal of Psychiatry.

[135]  G. Pearlson,et al.  Clinical phenotypes of psychosis in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). , 2013, The American journal of psychiatry.

[136]  R. Buchanan,et al.  A separate disease within the syndrome of schizophrenia. , 2001, Archives of general psychiatry.

[137]  F. Jacques Defining the clinical course of multiple sclerosis: The 2013 revisions , 2015, Neurology.

[138]  T. Lataster,et al.  Evidence that onset of psychosis in the population reflects early hallucinatory experiences that through environmental risks and affective dysregulation become complicated by delusions. , 2012, Schizophrenia bulletin.

[139]  L. Krabbendam,et al.  Does urbanicity shift the population expression of psychosis? , 2004, Journal of psychiatric research.